Anti-Aggregation Effects of Phenolic Compounds on α-Synuclein

The aggregation and deposition of α-synuclein (αS) are major pathologic features of Parkinson\u27s disease, dementia with Lewy bodies, and other α-synucleinopathies. The propagation of αS pathology in the brain plays a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that attenuate αS aggregation and propagation. Based on cumulative evidence that αS oligomers are neurotoxic and critical species in the pathogenesis of α-synucleinopathies, we and other groups reported that phenolic compounds inhibit αS aggregation including oligomerization, thereby ameliorating αS oligomer-induced cellular and synaptic toxicities. Heterogeneity in gut microbiota may influence the efficacy of dietary polyphenol metabolism. Our recent studies on the brain-penetrating polyphenolic acids 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-hydroxyphenylacetic acid (3-HPPA), which are derived from gut microbiota-based metabolism of dietary polyphenols, demonstrated an in vitro ability to inhibit αS oligomerization and mediate aggregated αS-induced neurotoxicity. Additionally, 3-HPPA, 3,4-diHBA, 3-HBA, and 4-hydroxybenzoic acid significantly attenuated intracellular αS seeding aggregation in a cell-based system. This review focuses on recent research developments regarding neuroprotective properties, especially anti-αS aggregation effects, of phenolic compounds and their metabolites by the gut microbiome, including our findings in the pathogenesis of α-synucleinopathies

Gut Microbiome-Modified Polyphenolic Compounds Inhibit α-Synuclein Seeding and Spreading in α-Synucleinopathies

Misfolding, aggregation and deposition of α-synuclein (α-syn) are major pathologic characteristics of Parkinson’s disease (PD) and the related synucleinopathy, multiple system atrophy (MSA). The spread of α-syn pathology across brain regions is thought to play a key role in the onset and progression of clinical phenotypes. Thus, there is increasing interest in developing strategies that target and attenuate α-syn aggregation and spread. Recent studies of brain-penetrating polyphenolic acids, namely, 3-hydroxybenzoic acid (3-HBA), 3,4-dihydroxybenzoic acid (3,4-diHBA), and 3-(3-hydroxyphenyl)propionic acid (3-HPPA) that are derived from gut microbiota metabolism of dietary polyphenols, show in vitro ability to effectively modulate α-syn misfolding, oligomerization, and mediate aggregated α-syn neurotoxicity. Here we investigate whether 3-HBA, 4-hydroxybenzoic acid (4-HBA), 3,4-diHBA, or 3-HPPA interfere with α-syn spreading in a cell-based system. Using HEK293 cells overexpressing α-syn-A53T-CFP/YFP, we assessed α-syn seeding activity using Fluorescence Resonance Energy Transfer (FRET) to detect and quantify α-syn aggregation. We demonstrated that 3-HPPA, 3,4-diHBA, 3-HBA, and 4-HBA significantly attenuated intracellular α-syn seeding aggregation. To determine whether our compounds could inhibit brain-derived seeding activity, we utilized insoluble α-syn extracted from post-mortem MSA or PD brain specimens. We found that 3-HPPA effectively attenuated MSA-induced aggregation of monomer into high molecular weight aggregates capable of inducing intracellular aggregation. Outcomes from our studies suggest interactions between gut microbiome and certain dietary factors may form the basis for effective therapies that modulate pathologic α-syn propagation. Collectively, our findings provide the basis for future developments of probiotic, prebiotic, or synbiotic approaches for modulating the onset and/or progression of α-synucleinopathies

Surface-sensitive NMR in optically pumped semiconductors

We present a scheme of surface-sensitive nuclear magnetic resonance in optically pumped semiconductors, where an NMR signal from a part of the surface of a bulk compound semiconductor is detected apart from the bulk signal. It utilizes optically oriented nuclei with a long spin-lattice relaxation time as a polarization reservoir for the second (target) nuclei to be detected. It provides a basis for the nuclear spin polarizer [IEEE Trans. Appl. Supercond. 14, 1635 (2004)], which is a polarization reservoir at a surface of the optically pumped semiconductor that polarizes nuclear spins in a target material in contact through the nanostructured interfaces.Comment: 4 pages, 5 figure

Origin for the enhanced copper spin echo decay rate in the pseudogap regime of the multilayer high-T_c cuprates

We report measurements of the anisotropy of the spin echo decay for the inner layer Cu site of the triple layer cuprate, Hg_0.8Re_0.2Ba_2Ca_2Cu_3O_8 (T_c=126 K) in the pseudogap T regime below T_pg ~ 170 K and the corresponding analysis for their interpretation. As the field alignment is varied, the shape of the decay curve changes from Gaussian (H_0 \parallel c) to single exponential (H_0 \perp c). The latter characterizes the decay caused by the fluctuations of adjacent Cu nuclear spins caused by their interactions with electron spins. The angular dependence of the second moment (T_{2M}^{-2} \equiv ) deduced from the decay curves indicates that T_{2M}^{-2} for H_0 \parallel c, which is identical to T_{2G}^{-2} (T_{2G} is the Gaussian component), is substantially enhanced, as seen in the pseudogap regime of the bilayer systems. Comparison of T_{2M}^{-2} between H_0 \parallel c and H_0 \perp c indicates that this enhancement is caused by electron spin correlations between the inner and the outer CuO_2 layers. These results provide the answer to the long-standing controversy regarding the opposite T dependences of (T_1T)^{-1} and T_{2G}^{-2} in the pseudogap regime of bi- and trilayer systems.Comment: 4 pages, 4 figure

Facilitating Constructive Discussions of Difficult Socio-Scientific Issues

Discussion can be an important and powerful tool in efforts to build a more diverse, equitable, and inclusive future for STEM (i.e., science, technology, engineering, and mathematics). However, facilitating discussions on difficult, complex, and often uncomfortable issues, like racism and sexism, can feel daunting. We outline a series of steps that can be used by educators to facilitate productive discussions that empower everyone to listen, contribute, learn, and ultimately act to transform STEM

A switchable controlled-NOT gate in a spin-chain NMR quantum computer

A method of switching a controlled-NOT gate in a solid-stae NMR quantum computer is presented. Qubits of I=1/2 nuclear spins are placed periodically along a quantum spin chain (1-D antiferromagnet) having a singlet ground state with a finite spin gap to the lowest excited state caused by some quantum effect. Irradiation of a microwave tuned to the spin gap energy excites a packet of triplet magnons at a specific part of the chain where control and target qubits are involved. The packet switches on the Suhl-Nakamura interaction between the qubits, which serves as a controlled NOT gate. The qubit initialization is achieved by a qubit initializer consisting of semiconducting sheets attached to the spin chain, where spin polarizations created by the optical pumping method in the semiconductors are transferred to the spin chain. The scheme allows us to separate the initialization process from the computation, so that one can optimize the computation part without being restricted by the initialization scheme, which provides us with a wide selection of materials for a quantum computer.Comment: 8 pages, 5 figure

Analysis of bis(trifluoromethylsulfonyl)imide-doped paramagnetic graphite intercalation compound using F-19 very fast magic angle spinning nuclear magnetic resonance

F atoms bonding to paramagnetic/conductive graphene layers in accepter-type graphite intercalation compounds (GICs) are analyzed using very fast magic angle spinning nuclear magnetic resonance, which is applied for the first time on F-19 nuclei to investigate paramagnetic materials. In the bis(trifluoromethylsulfonyl)imide(TFSI)-doped GIC, C-F bonds between fluorine atoms and graphene layers conform to a weak bonding of F to the graphene sheets. TFSI anions intercalated in the GIC do not show overall molecular motion; even at room temperature only the CF3 groups rotate